Proteolisis endotelial inducida por la proteína c reactiva: implicaciones en pacientes con aterosclerosis
- Autores: Ines Montero Garcia Siso
- Directores de la Tesis: José Antonio Páramo Fernández (dir. tes.), Josune Orbe (codir. tes.)
- Lectura: En la Universidad de Navarra ( España ) en 2005
- Idioma: español
- Tribunal Calificador de la Tesis: Melchor Álvarez de Mon Soto (presid.), Miguel-Ángel Idoate (secret.), Fernando Civeira Murillo (voc.), Francisco Velasco Gimena (voc.), Oscar Beloqui Ruiz (voc.)
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- Resumen
TITULO: PROTEOLISIS ENDOTELIAL INDUCIDA POR LA PROTEINA C REACTIVA: IMPLICACIONES EN PACIENTES CON ATEROSCLEREOSIS RESUMEN: INTR0DUCTI0NCreactive protein (CRP) may play a direct role in atherosclerosis. We examined the effect of CRP on the expression of matrix metalloproteinases (mmps) and their inhibitors (TlMPs) in human umbilical vein endothelial cells (huvec) and in patients with atherosclerosis.
METHODS and results huvec (n=4) were incubated in presence or absence of CRP (50ug/mL, 12h). Real-time PCR and immunological assays were performed to investigate changes in MMP expression. Exposure to CRP augmented MMP-1 and mmp-10 mRNA expression by HUVEC (2.3±0.6-fold and 4.2±1.4-fold change respectively, both P<0.05) and increased total MMP-1 and MMP-10 protein (by 1.5±0.1 and 2.8±0.2-fold respectively, both P<0.001), as well as the proportion active protein/zymogen (by 1.5±0.5 and 2.2±0.7-fold respectively; both P<0.05), suggesting increased proteolytic activation. MMP-l and MMP-10 plasma levies were also measured in asymptomatic subjects (n=70) with cardiovascular risk factors, stratified according to their serum hs-CRP (cut-off 3mg/L). Both MMP-1 and MMP-10 were significantly increased in patients with high hs-CRP (n=37) compared with the remaining subjects (both P<0.05). The association of hs-CRP and both MMP-1 and MMP-10 remained significant after adjustment for cardiovascular risk factors (both P<0.05).-ln addition, MMP-10 correlated with carotid intima-media thickness (P<0.05), suggesting a relation of proteolysis and subclinical atherosclerosis. Finally, both CRP and MMP-10, assessed by confocal microscopy and immunohistochemistry, colocalized in endothelial cells and macrophage-rich areas of advanced atherosclerotic plaques from patients who underwent carotid endarterectomy (n=15). CONCLUSlONS increased local and systemic CRP-related MMP-1 and MMP-10 activation might provide new mechanistic insights linking inflammation to plaque vulnerability.
